24-hour human urine and serum profiles of bisphenol A: Evidence against sublingual absorption following ingestion in soup.
نویسندگان
چکیده
Extensive first-pass metabolism of ingested bisphenol A (BPA) in the gastro-intestinal tract and liver restricts blood concentrations of bioactive BPA to <1% of total BPA in humans and non-human primates. Absorption of ingested BPA through non-metabolizing tissues of the oral cavity, recently demonstrated in dogs, could lead to the higher serum BPA concentrations reported in some human biomonitoring studies. We hypothesized that the extensive interaction with the oral mucosa by a liquid matrix, like soup, relative to solid food or capsules, might enhance absorption through non-metabolizing oral cavity tissues in humans, producing higher bioavailability and higher serum BPA concentrations. Concurrent serum and urine concentrations of d6-BPA, and its glucuronide and sulfate conjugates, were measured over a 24hour period in 10 adult male volunteers following ingestion of 30μg d6-BPA/kg body weight in soup. Absorption of d6-BPA was rapid (t1/2=0.45h) and elimination of the administered dose was complete 24h post-ingestion, evidence against any tissue depot for BPA. The maximum serum d6-BPA concentration was 0.43nM at 1.6h after administration and represented <0.3% of total d6-BPA. Pharmacokinetic parameters, pharmacokinetic model simulations, and the significantly faster appearance half-life of d6-BPA-glucuronide compared to d6-BPA (0.29h vs 0.45h) were evidence against meaningful absorption of BPA in humans through any non-metabolizing tissue (<1%). This study confirms that typical exposure to BPA in food produces picomolar to subpicomolar serum BPA concentrations in humans, not nM concentrations reported in some biomonitoring studies.
منابع مشابه
24-hour human urine and serum profiles of bisphenol A following ingestion in soup: Individual pharmacokinetic data and emographics
Here we present data to evaluate potential absorption of Bisphenol A through non-metabolizing tissues of the upper digestive tract. Concurrent serum and urine concentrations of d6-BPA, and its glucuronide and sulfate conjugates, were measured over a 24 h period in 10 adult male volunteers following ingestion of 30 μg d6-BPA/kg body weight in soup. The pharmacokinetic behavior of BPA and its met...
متن کاملExposure Conditions and Pharmacokinetic Principles: Interpreting Bisphenol A Absorption in the Canine Oral Cavity
Gayrard et al. (2013) reported significant (~ 80%) absorption of bisphenol A (BPA) from solutions applied to the oral cavity of dogs, leading to higher serum BPA (aglycone) concentrations than occurred when BPA was absorbed through the gastro intestinal tract. This finding is consistent with first prin ciples and experience with orally absorbed drugs. The implications for human exposure and he...
متن کاملInterpreting Bisphenol A Absorption in the Canine Oral Cavity: Gayrard et al. Respond
Gayrard et al. (2013) reported significant (~ 80%) absorption of bisphenol A (BPA) from solutions applied to the oral cavity of dogs, leading to higher serum BPA (aglycone) concentrations than occurred when BPA was absorbed through the gastro intestinal tract. This finding is consistent with first prin ciples and experience with orally absorbed drugs. The implications for human exposure and he...
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A previously developed physiologically based pharmacokinetic (PBPK) model for bisphenol A (BPA) in adult rhesus monkeys was modified to characterize the pharmacokinetics of BPA and its phase II conjugates in adult humans following oral ingestion. Coupled with in vitro studies on BPA metabolism in the liver and the small intestine, the PBPK model was parameterized using oral pharmacokinetic data...
متن کاملHigh Bioavailability of Bisphenol A from Sublingual Exposure
BACKGROUND Bisphenol A (BPA) risk assessment is currently hindered by the rejection of reported higher-than-expected plasma BPA concentrations in humans after oral ingestion. These are deemed incompatible with the almost complete hepatic first-pass metabolism of BPA into its inactive glucurono-conjugated form, BPA glucuronide (BPAG). OBJECTIVES Using dogs as a valid model, we compared plasma ...
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ورودعنوان ژورنال:
- Toxicology and applied pharmacology
دوره 288 2 شماره
صفحات -
تاریخ انتشار 2015